A monkey model of exercise-induced reproductive dysfunction, in which female monkeys (Macaca ascicularis exercise daily on treadmills, has been developed by this laboratory. The primary goal of this grant is to use this model to elucidate the physiological mechanisms by which chronic exercise leads to an interruption of normal reproductive function in this representative primate species. A secondary objective is to determine if there are factors which predispose an individual to exercise-induced reproductive dysfunction. Knowledge of such factors would allow clinicians to encourage individuals to participate in sports and exercise programs for the many clinical benefits of regular exercise (such as improved cardiovascular and respiratory health), while providing them with information on how to minimize the possible adversities of exercise training (such as decreased fertility, and decreased reproductive hormone secretion leading to lower bone density and possible cardiovascular and cancer risks). In addition, it is expected that the proposed studies will provide information relevant to other physiological and pathological situations (including normal childhood, undernutrition, anorexia nervosa, spontaneous hypothalamic-hypophyseal dysfunction and stress), in which normal reproductive function is also thought to be suppressed by a failure of the GnRH-containing neurons in the hypothalamus to adequately stimulate pituitary gonadotropin release. The first specific aim of this grant is to determine whether metabolic adaptation to vigorous exercise training provides the "signal" which suppresses central drive to the reproductive axis. Experiments will measure changes in metabolic rate and fitness level throughout the course of training and determine if changes in these parameters correlate with the development of reproductive dysfunction. Additional experiments will test whether reversal of metabolic changes that occur with exercise training can restore normal reproductive function. The second specific aim of this grant is to determine whether changes in the activity of central neuronal systems that project onto GnRH neurons cause exercise-induced reproductive dysfunction by measuring changes in CSF neurotransmitter levels and neurotransmitter gene expression with exercise training, and then testing whether pharmacological reversal of changes in specific neurotransmitter systems will correct exercise-induced amenorrhea. The third specific aim is to determine whether the following parameters are predisposing factors which alter the susceptibility to exercise-induced reproductive dysfunction: the intensity of exercise training, the body composition of the individual, whether the individual "likes" exercise training or feels the training is "stressful," and the age of the individual during exercise training.